To understand how the nervous system controls complex motor acts it is necessary to determine the properties of the neural and muscular elements that produce a particular act. For a few behaviors in invertebrates, all or most of the neural and muscular elements that make up the behavioral control system have been identified and characterized. These control systems are not static; neuromodulatory and neurohumoral influences constantly fine-tune both the neural and muscular components of these systems to meet the demand of the animal's changing internal and external environment. It is necessary to explore these tuning mechanisms to further our understanding of how neural and muscular systems produce environmentally relevant behavior. Concentrating on the well-defined behavioral control systems of invertebrates will ensure progress toward this goal. The heartbeat control system of the leech has emerged as a promising system for study. The system includes well-defined central pattern generating network of heart interneurons. This network elaborates a complex pattern of rhythmic activity that is imposed on segmental heart motor neurons. The heart motor neurons then impose their rhythmicity on the hearts of entraining their myogenic rhythms. At every level within the system there are modulatory influences that can be ascribed to identified neurons. In this application we propose to study modulatory influences on the heartbeat control system and other motor systems of the leech. We propose to confirm our immunohistochemical evidence that the neuromodulatory peptides proctolin and FMRFamide, or related peptides, are present in the central nervous system (CNS) of the leech, and to explore their effects on the heartbeat control system and other motor systems. These studies will develop the leech into a preparation where peptidergic neurotransmission can be studied in a behaviorally relevant context. By studying the effects of peptides in such a system important insight into the role of peptide neuromodulators in the nervous system will emerge that can contribute to our knowledge of how the nervous system malfunctions in disease states.